PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity. / van Setten, Jessica; Brody, Jennifer A; Jamshidi, Yalda; Swenson, Brenton R; Butler, Anne M; Campbell, Harry; Del Greco, Fabiola M; Evans, Daniel S; Gibson, Quince; Gudbjartsson, Daniel F; Kerr, Kathleen F; Krijthe, Bouwe P; Lyytikäinen, Leo-Pekka; Müller, Christian; Müller-Nurasyid, Martina; Nolte, Ilja M; Padmanabhan, Sandosh; Ritchie, Marylyn D; Robino, Antonietta; Smith, Albert V; Steri, Maristella; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; Ulivi, Sheila; Verweij, Niek; Yin, Xiaoyan; Arnar, David O; Asselbergs, Folkert W; Bader, Joel S; Barnard, John; Bis, Josh; Blankenberg, Stefan; Boerwinkle, Eric; Bradford, Yuki; Buckley, Brendan M; Chung, Mina K; Crawford, Dana; den Hoed, Marcel; Denny, Josh C; Dominiczak, Anna F; Ehret, Georg B; Eijgelsheim, Mark; Ellinor, Patrick T; Felix, Stephan B; Franco, Oscar H; Franke, Lude; Harris, Tamara B; Holm, Hilma; Ilaria, Gandin; Iorio, Annamaria; Kähönen, Mika; Kolcic, Ivana; Kors, Jan A; Lakatta, Edward G; Launer, Lenore J; Lin, Honghuang; Lin, Henry J; Loos, Ruth J F; Lubitz, Steven A; Macfarlane, Peter W; Magnani, Jared W; Leach, Irene Mateo; Meitinger, Thomas; Mitchell, Braxton D; Munzel, Thomas; Papanicolaou, George J; Peters, Annette; Pfeufer, Arne; Pramstaller, Peter P; Raitakari, Olli T; Rotter, Jerome I; Rudan, Igor; Samani, Nilesh J; Schlessinger, David; Silva Aldana, Claudia T; Sinner, Moritz F; Smith, Jonathan D; Snieder, Harold; Soliman, Elsayed Z; Spector, Timothy D; Stott, David J; Strauch, Konstantin; Tarasov, Kirill V; Thorsteinsdottir, Unnur; Uitterlinden, Andre G; Van Wagoner, David R; Völker, Uwe; Völzke, Henry; Waldenberger, Melanie; Jan Westra, Harm; Wild, Philipp S; Zeller, Tanja; Alonso, Alvaro; Avery, Christy L; Bandinelli, Stefania; Benjamin, Emelia J; Cucca, Francesco; Dörr, Marcus; Ferrucci, Luigi; Gasparini, Paolo; Gudnason, Vilmundur; Hayward, Caroline; Heckbert, Susan R; Hicks, Andrew A; Jukema, J Wouter; Kääb, Stefan; Lehtimäki, Terho; Liu, Yongmei; Munroe, Patricia B; Parsa, Afshin; Polasek, Ozren; Psaty, Bruce M; Roden, Dan M; Schnabel, Renate B; Sinagra, Gianfranco; Stefansson, Kari; Stricker, Bruno H; van der Harst, Pim; van Duijn, Cornelia M; Wilson, James F; Gharib, Sina A; de Bakker, Paul I W; Isaacs, Aaron; Arking, Dan E; Sotoodehnia, Nona.
In: NAT COMMUN, Vol. 9, No. 1, 25.07.2018, p. 2904.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
AU - van Setten, Jessica
AU - Brody, Jennifer A
AU - Jamshidi, Yalda
AU - Swenson, Brenton R
AU - Butler, Anne M
AU - Campbell, Harry
AU - Del Greco, Fabiola M
AU - Evans, Daniel S
AU - Gibson, Quince
AU - Gudbjartsson, Daniel F
AU - Kerr, Kathleen F
AU - Krijthe, Bouwe P
AU - Lyytikäinen, Leo-Pekka
AU - Müller, Christian
AU - Müller-Nurasyid, Martina
AU - Nolte, Ilja M
AU - Padmanabhan, Sandosh
AU - Ritchie, Marylyn D
AU - Robino, Antonietta
AU - Smith, Albert V
AU - Steri, Maristella
AU - Tanaka, Toshiko
AU - Teumer, Alexander
AU - Trompet, Stella
AU - Ulivi, Sheila
AU - Verweij, Niek
AU - Yin, Xiaoyan
AU - Arnar, David O
AU - Asselbergs, Folkert W
AU - Bader, Joel S
AU - Barnard, John
AU - Bis, Josh
AU - Blankenberg, Stefan
AU - Boerwinkle, Eric
AU - Bradford, Yuki
AU - Buckley, Brendan M
AU - Chung, Mina K
AU - Crawford, Dana
AU - den Hoed, Marcel
AU - Denny, Josh C
AU - Dominiczak, Anna F
AU - Ehret, Georg B
AU - Eijgelsheim, Mark
AU - Ellinor, Patrick T
AU - Felix, Stephan B
AU - Franco, Oscar H
AU - Franke, Lude
AU - Harris, Tamara B
AU - Holm, Hilma
AU - Ilaria, Gandin
AU - Iorio, Annamaria
AU - Kähönen, Mika
AU - Kolcic, Ivana
AU - Kors, Jan A
AU - Lakatta, Edward G
AU - Launer, Lenore J
AU - Lin, Honghuang
AU - Lin, Henry J
AU - Loos, Ruth J F
AU - Lubitz, Steven A
AU - Macfarlane, Peter W
AU - Magnani, Jared W
AU - Leach, Irene Mateo
AU - Meitinger, Thomas
AU - Mitchell, Braxton D
AU - Munzel, Thomas
AU - Papanicolaou, George J
AU - Peters, Annette
AU - Pfeufer, Arne
AU - Pramstaller, Peter P
AU - Raitakari, Olli T
AU - Rotter, Jerome I
AU - Rudan, Igor
AU - Samani, Nilesh J
AU - Schlessinger, David
AU - Silva Aldana, Claudia T
AU - Sinner, Moritz F
AU - Smith, Jonathan D
AU - Snieder, Harold
AU - Soliman, Elsayed Z
AU - Spector, Timothy D
AU - Stott, David J
AU - Strauch, Konstantin
AU - Tarasov, Kirill V
AU - Thorsteinsdottir, Unnur
AU - Uitterlinden, Andre G
AU - Van Wagoner, David R
AU - Völker, Uwe
AU - Völzke, Henry
AU - Waldenberger, Melanie
AU - Jan Westra, Harm
AU - Wild, Philipp S
AU - Zeller, Tanja
AU - Alonso, Alvaro
AU - Avery, Christy L
AU - Bandinelli, Stefania
AU - Benjamin, Emelia J
AU - Cucca, Francesco
AU - Dörr, Marcus
AU - Ferrucci, Luigi
AU - Gasparini, Paolo
AU - Gudnason, Vilmundur
AU - Hayward, Caroline
AU - Heckbert, Susan R
AU - Hicks, Andrew A
AU - Jukema, J Wouter
AU - Kääb, Stefan
AU - Lehtimäki, Terho
AU - Liu, Yongmei
AU - Munroe, Patricia B
AU - Parsa, Afshin
AU - Polasek, Ozren
AU - Psaty, Bruce M
AU - Roden, Dan M
AU - Schnabel, Renate B
AU - Sinagra, Gianfranco
AU - Stefansson, Kari
AU - Stricker, Bruno H
AU - van der Harst, Pim
AU - van Duijn, Cornelia M
AU - Wilson, James F
AU - Gharib, Sina A
AU - de Bakker, Paul I W
AU - Isaacs, Aaron
AU - Arking, Dan E
AU - Sotoodehnia, Nona
PY - 2018/7/25
Y1 - 2018/7/25
N2 - Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
AB - Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
KW - Atrial Function/physiology
KW - Atrioventricular Node/physiology
KW - Electrocardiography
KW - Electrophysiological Phenomena/genetics
KW - Female
KW - Genome-Wide Association Study
KW - Humans
KW - Linkage Disequilibrium/genetics
KW - Male
KW - Mutation, Missense/genetics
KW - Risk Factors
U2 - 10.1038/s41467-018-04766-9
DO - 10.1038/s41467-018-04766-9
M3 - SCORING: Journal article
C2 - 30046033
VL - 9
SP - 2904
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -